Is PCNT p.Pro2329Arg (c.6986C>G) pathogenic?

PCNT p.Pro2329Arg (c.6986C>G) is classified Benign/Likely benign in PCNT (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.1179); Low-frequency (popmax 1.49%, afr); Associated with microcephalic osteodysplastic primordial dwarfism type II.

What condition is associated with PCNT p.Pro2329Arg (c.6986C>G)?

PCNT p.Pro2329Arg (c.6986C>G) is associated with microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

How common is PCNT p.Pro2329Arg (c.6986C>G) in the general population?

PCNT p.Pro2329Arg (c.6986C>G) is low-frequency (popmax 1.49%, afr) (gnomAD).

What do computational predictors say about PCNT p.Pro2329Arg (c.6986C>G)?

AlphaMissense predicts likely benign (score 0.1179) — an in-silico prediction, not a clinical call.

PCNT p.Pro2329Arg

c.6986C>G · rs35848602 · VCV159647

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.1179 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.49%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

microcephalic osteodysplastic primordial dwarfism type II

Computational evidence

Protein change
AlphaMissense	0.1179	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 0.59, phastCons 0.57
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.027 · regional, not allelic
Overall
CADD	18.19	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.49% African / African-American · 1,115/74,864 alleles

Filtering AF 1.42% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.39%

Overall 0.189% 3,040/1,608,660 alleles · low-frequency exomes 2,130/1,456,340 · genomes 910/152,320 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.51%	66
African / African-Americangrpmax	1.49%	67
Middle Eastern	0.81%	123
Admixed American	0.493%	203
Remaining individualsnot grpmax-eligible	0.387%	259
European (non-Finnish)	0.075%	1,334
South Asian	0.0088%	11,369
Finnishnot grpmax-eligible	0.00312%	32,014

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PCNT
Protein: p.Pro2329Arg
Coding: c.6986C>G
MANE Select: NM_006031
dbSNP: rs35848602
Type: single nucleotide variant
Location: chr21:46418268 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Residue 2329: a UniProt-annotated variant site (in); the 'disordered' region

Full PCNT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

microcephalic osteodysplastic primordial dwarfism type II — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PCNT c.1032+1G>A Pathogenic/Likely pathogenic ★★ same condition
PCNT c.1680-1G>C Likely pathogenic ★★ same condition
PCNT c.5995-2A>C Likely pathogenic ★★ same condition
PCNT c.7024+1G>C Likely pathogenic ★★ same condition
PCNT c.7691-1G>A Likely pathogenic ★★ same condition
PCNT c.9624-2A>G Likely pathogenic ★★ same condition
PCNT p.Arg1730Ter Pathogenic/Likely pathogenic ★★ same condition
PCNT p.Arg1923Ter Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/pcnt-p-pro2329arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown